Studies have continued to determine the molecular forms and cellular targets of estrogenic chemicals and establish the mechanisms by which interactions of estrogens with developing genital tract target cells result in permanently altered differentiation, including neoplasia. In the period covered by the report, the ovary and oviduct have been clearly established as targets for diethylstilbestrol (DES)-induced dysmorphogenesis. The cellular alterations in the ovary are associated with functional defects--altered steroidgenesis. The epithelial cells of the oviduct no longer maintain appropriate growth controls. Experiments in vitro with the fetal anlage of reproductive tract tissues, the Mullerian duct, have demonstrated that the fetal tract is imprinted by DES at the molecular level and becomes unresponsive to its normal tissue effector, Mullerian Inhibiting Factor. Futhermore, the fetal genital tract is capable of oxidatively metabolizing DES along pathways which generate reactive intermediates. This may play a role in the long-term dysdifferentiation of those target tissues, since DES metabolism has been also associated with genetic alteration in model cells in culture (Syrian hamster embryo fibroblasts) including aneuploidy induction and unscheduled DNA synthesis. These occurred under conditions associated with neoplastic transformation of cells in vitro.